3-Phenylpiperidines. Central dopamine-autoreceptor stimulating activity.
Thirty compounds related to the selective dopamine-autoreceptor agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine have been synthesized and tested for central dopamine-autoreceptor stimulating activity. The 3-(3-hydroxyphenyl)piperidine moiety seems indispensable for high potency and selectivity. Introduction of an additional hydroxyl group into the 4 position of the aromatic ring gives a compound with dopaminergic activity but lacking selectivity for autoreceptors. 3-(3-Hydroxyphenyl)-N-n-propylpyrrolidine, 3-(3-hydroxy)-N-n-propylperhydroazepine, and 3-(3-hydroxyphenyl)quinuclidine were all inactive. The most potent compounds were the N-isopropyl-, N-n-butyl-, N-n-pentyl-, and N-phenethyl-substituted 3-(3-hydroxyphenyl)piperidine derivatives. None of the compounds investigated seemed to have central noradrenaline- or serotonin-receptor stimulating activity.
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects*; D055598:Chemical Phenomena; D002621:Chemistry; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004347:Drug Interactions; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013268:Stimulation, Chemical
D010880:Piperidines; D011954:Receptors, Dopamine; D004295:Dihydroxyphenylalanine; D006916:5-Hydroxytryptophan; D001058:Apomorphine